rs376777147

Variant names:

• chr8-56316157-C-G
• rs376777147
• NM_138969.4:c.191G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-56316157-C-G
• chr8-56316157-C-A
• chr8-56316157-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_138969.4(SDR16C5):​c.191G>C​(p.Gly64Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: SDR16C5 NM_138969.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.22
• Publications: 0 publications found

Genes affected

SDR16C5 (HGNC:30311): (short chain dehydrogenase/reductase family 16C member 5) This gene encodes a member of the short-chain alcohol dehydrogenase/reductase superfamily of proteins and is involved in the oxidation of retinol to retinaldehyde. The encoded protein is associated with the endoplasmic reticulum and is predicted to contain three transmembrane helices, suggesting that it is an integral membrane protein. It recognizes all-trans-retinol and all-trans-retinaldehyde as substrates and exhibits a strong preference for NAD(+)/NADH as cofactors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.803

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138969.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDR16C5	NM_138969.4	MANE Select	c.191G>C	p.Gly64Ala	missense	Exon 2 of 7	NP_620419.2
	SDR16C5	NM_001318049.2		c.191G>C	p.Gly64Ala	missense	Exon 2 of 8	NP_001304978.1	G3V145
	SDR16C5	NM_001318050.2		c.191G>C	p.Gly64Ala	missense	Exon 2 of 6	NP_001304979.1	Q8N3Y7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDR16C5	ENST00000303749.8	TSL:1 MANE Select	c.191G>C	p.Gly64Ala	missense	Exon 2 of 7	ENSP00000307607.3	Q8N3Y7-1
	SDR16C5	ENST00000396721.6	TSL:1	c.191G>C	p.Gly64Ala	missense	Exon 2 of 6	ENSP00000379947.2	Q8N3Y7-2
	SDR16C5	ENST00000522671.1	TSL:2	c.191G>C	p.Gly64Ala	missense	Exon 2 of 8	ENSP00000431010.1	G3V145

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251476 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000246 AC: 36 AN: 1461850 Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16 AN XY: 727232

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1111982

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74342

African (AFR) AF: 0.0000241 AC: 1 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.81	D
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.97	D
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		3.2
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.54
MVP		0.97
MPC		0.29
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.36
gMVP		0.81
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs376777147; hg19: chr8-57228716;